The goal of this project is the understanding of mechanisms of demyelination occurring in the CNS during viral infections and in experimental allergic encephalomyelitis (EAE). Mechanisms of immunity may be important at two levels: (1) in relation to resistance to viral infection, and (2) in relation to immunemediated demyelination directed toward viral antigens or self antigens such as myelin basic protein (MBP). The viral infection of the CNS which has been utilized is that of Herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) in C57/B16 mice. The first phase of this work has concentrated on the immunocytochemical detection of HSV antigens. To this end, we have prepared rabbit antisera to HSV-1 and HSV-2 for use in the peroxidase-antiperoxidase (PAP) and biotinavidin immunocytochemical technique. The antisera can distinguish the two types of HSV in paraffin sections of formalin-fixed infected mouse CNS without prior absorption of the serum by the heterologous viral type. Also, antisera prepared to RK-13 cells infected for 4 or 8 hours with HSV-1 detect preferentially cytoplasmic antigen, whereas antisera to 18-hour infected RK-13 cells detect primarily nuclear antigen. With these sera expression of viral antigens will be studied in the CNS of normal unimmunized mice and in mice immunized with the homologous or heterologous HSV type. The second aspect of this study concerns the structure and function of MBP in myelin and the effects of viral infection or autoimmunity on its synthesis and incorporation into myelin. A model for MBP structure based on the known amino acid sequence has been proposed. The model suggests that phosphorylation of certain Thr and Ser residues in the nascent polypeptide plays an important role during folding into the native structure of the protein in myelin. Clearly, interference with synthesis or processing of an essential protein such as MBP by virally-induced alteration of cellular functions might seriously compromise the capacity of oligodendrocytes to synthesize and maintain myelin. Elucidation of the molecular mechanisms which may be operative in a demyelinating disease such as multiple sclerosis is the ultimate goal of this investigation.